|ZFIN ID: ZDB-PUB-170810-6|
Comprehensive validation of T- and B-cell deficiency in rag1-null zebrafish: Implication for the robust innate defense mechanisms of teleosts
Tokunaga, Y., Shirouzu, M., Sugahara, R., Yoshiura, Y., Kiryu, I., Ototake, M., Nagasawa, T., Somamoto, T., Nakao, M.
|Source:||Scientific Reports 7: 7536 (Journal)|
|Keywords:||Innate immunity, Innate lymphoid cells, VDJ recombination|
|PubMed:||28790360 Full text @ Sci. Rep.|
Tokunaga, Y., Shirouzu, M., Sugahara, R., Yoshiura, Y., Kiryu, I., Ototake, M., Nagasawa, T., Somamoto, T., Nakao, M. (2017) Comprehensive validation of T- and B-cell deficiency in rag1-null zebrafish: Implication for the robust innate defense mechanisms of teleosts. Scientific Reports. 7:7536.
ABSTRACTrag1 -/- zebrafish have been employed in immunological research as a useful immunodeficient vertebrate model, but with only fragmentary evidence for the lack of functional adaptive immunity. rag1-null zebrafish exhibit differences from their human and murine counterparts in that they can be maintained without any specific pathogen-free conditions. To define the immunodeficient status of rag1 -/- zebrafish, we obtained further functional evidence on T- and B-cell deficiency in the fish at the protein, cellular, and organism levels. Our developed microscale assays provided evidence that rag1 -/- fish do not possess serum IgM protein, that they do not achieve specific protection even after vaccination, and that they cannot induce antigen-specific CTL activity. The mortality rate in non-vaccinated fish suggests that rag1 -/- fish possess innate protection equivalent to that of rag1 +/- fish. Furthermore, poly(I:C)-induced immune responses revealed that the organ that controls anti-viral immunity is shifted from the spleen to the hepatopancreas due to the absence of T- and B-cell function, implying that immune homeostasis may change to an underside mode in rag-null fish. These findings suggest that the teleost relies heavily on innate immunity. Thus, this model could better highlight innate immunity in animals that lack adaptive immunity than mouse models.